U.S gives green signal for the first CRISPR human clinical trial

In the public realm, opinions about CRISPR have ranged from those that are exhilarated by its potential, to others that are terrified of the implications of the technology, often equating it to be an attempt to play God. While the changing nature of scientific knowledge is a constant, perhaps a more static constant has been the mix of fascination and fear that greets each innovation. CRISPR has been no exception.

In the past 4 years, the final pieces of the CRISPR puzzle came together with the identification of various components such as crRNA, tracrRNA and the Cas9 nuclease and the harnessing of the technology for genome editing led to a wave of interest. The looming patent war between two competing groups did not do much to the eyeballs CRISPR-Cas9 was attracting.

The CRISPR-Cas9 system was originally discovered in bacteria as an immune system that adapts to invading phages by recording and creating a memory of the invasion in the genome of the host organism. This process was orchestrated by the DNA cleaving enzyme Cas9 nuclease. The significance of this was soon clear, as the potential of Cas9 nuclease to be programmed became clear. Different groups around the world have programmed Cas9 to exploit its DNA cleaving ability to edit the genome. This area of research has rapidly expanded with groups successfully achieving gene editing and knockdown in numerous in vitro biological models. Scientists have also tried to use the system to modify living cells in vivo. A remarkable feat, considering the time frame.

The Next Big Thing?

On the 21st of June, in perhaps a move, that is reminiscent of the rapid manner that the scientific community has taken to CRISPR-Cas9, an advisory committee at the National Institute of health approved a proposal that aims to use CRISPR–Cas9 genome editing technology to bolster immunotherapy.

Immunotherapy exploits the ability of the immune system to attack and kill cancer cells. The immune cells from the patient are taken, they are engineered to identify cancer cells as foreign entities. The engineered cells when injected back into the patient go about effectively killing the cancer cells.

This aggressive new therapy has now found a backer, someone, whose own aggressive venture capitalism has been the stuff of legends. The landmark proposal to use CRISPR-Cas9 for immunotherapy is backed by former Facebook President Sean Parker’s US$250 million, Parker Institute for Cancer Immunotherapy Foundation which was instituted in April 2016. This strategy has been hailed by the community as first of its kind to create a truly collaborative environment that has shown rapid advancements.

Following this win, the research team led by Edward Statdtmauer will start convincing the regulatory bodies at Stadtmauer’s University of Pennsylvania as well as other institutes participating in the study to allow the trial by the end of this year.This trial is small and designed to test whether CRISPR is safe for use in people, rather than whether it cures cancer or not. The prospective plan once armed with all the necessary approvals involves extracting T cells from 18 patients with myeloma, sarcoma or melanoma and altering them by CRISPR. The final product will have three edits in their genome that will enable them to detect cancer cells effectively. Once edited, the researchers will then infuse the edited cells back into the patient.

The ease with which CRISPR can be used to make multiple edits will be a major advantage for researchers and will advance cell therapy in a major way. Despite the ease of use offered by CRISPR to completely ablate gene expression, there have been concerns regarding the specificity and efficiency in practice.

A team of researchers at Massachusetts General Hospital and Harvard Medical School demonstrated that CRISPR-Cas9 had much high off-target to on-target ratio compared to older technologies such as ZFNs and TALENs. The heady environment and the excitement around this big win for cell therapy is heartening for researchers currently working on the project.

However, for the rest of the world, far removed from the action, it is time to wait and watch the next chapter in cell therapy unfold.

Shruti Srinivasan is a 4th year Ph.D. student at the National University of Singapore. In addition to Epigenetics, her primary research interest, she cares deeply about education, equal representation of women and healthcare. Shruti wishes to invest her time and effort advocating for these causes in the future. She is also interested in opportunities in life science consulting